Vous êtes sur la page 1sur 10

Green tea intake lowers fasting serum total and LDL cholesterol

in adults: a meta-analysis of 14 randomized controlled trials1–4

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


Xin-Xin Zheng, Yan-Lu Xu, Shao-Hua Li, Xu-Xia Liu, Rutai Hui, and Xiao-Hong Huang

ABSTRACT produced from fresh leaves of Camellia sinensis and is not


Background: The effect of green tea beverage and green tea extract traditionally fermented. Green tea contains antioxidants and
on lipid changes is controversial. other beneficial nutrients such as protein, carbohydrates, min-
Objective: We aimed to identify and quantify the effect of green tea erals, vitamins, and flavonoid-like polyphenols (4). Epidemio-
and its extract on total cholesterol (TC), LDL cholesterol, and HDL logic studies have reported an inverse relation between green tea
cholesterol. consumption and CVD risk. Subjects who drink .2 cups of
Design: We performed a comprehensive literature search to identify green tea/d had lower plasma total cholesterol (TC) concen-
relevant trials of green tea beverages and extracts on lipid profiles in trations and have been shown to reduce their risk of death from
adults. Weighted mean differences were calculated for net changes CVD by 22–33% (5, 6). In vivo and in vitro studies have shown
in lipid concentrations by using fixed-effects or random-effects that green tea catechins (which belong to the family of flavonols
models. Study quality was assessed by using the Jadad score, and and serve as an essential component of green tea), exert a car-
a meta-analysis was conducted. dioprotective effect via multiple mechanisms (7–10) including
Results: Fourteen eligible randomized controlled trials with 1136 the inhibition of oxidation, vascular inflammation, thrombo-
subjects were enrolled in our current meta-analysis. Green tea con- genesis, and improvement in blood lipid concentrations.
sumption significantly lowered the TC concentration by 7.20 mg/dL Recent animal studies have revealed that green tea catechins
(95% CI: 28.19, 26.21 mg/dL; P , 0.001) and significantly low- could inhibit key enzymes involved in lipid biosynthesis and
ered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: reduce the intestinal absorption of TC, thereby improving blood
23.16, 21.21 mg/dL; P , 0.001). The mean change in blood HDL- lipid profiles (9, 10). Because of promising results in preclinical
cholesterol concentration was not significant. Subgroup and sensi-
models, a substantial number of clinical trials have been per-
tivity analyses showed that these changes were not influenced by the
formed to investigate the effect of green tea beverages and
type of intervention, treatment dose of green tea catechins, study
extracts on lipid profiles of subjects with cardiovascular-related
duration, individual health status, or quality of the study. Overall, no
diseases as well as of healthy individuals (11–24). However,
significant heterogeneity was detected for TC, LDL cholesterol, and
results of these trials were inconsistent, and sample sizes were
HDL cholesterol; and results were reported on the basis of fixed-
relatively modest. As a result, the precise effect of green tea on
effects models.
Conclusion: The analysis of eligible studies showed that the adminis-
lipid profiles has not been established to our knowledge.
tration of green tea beverages or extracts resulted in significant reduc- Therefore, we conducted a meta-analysis of all published ran-
tions in serum TC and LDL-cholesterol concentrations, but no effect on domized controlled trials (RCTs) that investigated the effects of
HDL cholesterol was observed. Am J Clin Nutr 2011;94:601–10. green tea on blood cholesterol, including TC, LDL cholesterol,
and HDL cholesterol.

1
From the Key Laboratory for Clinical Cardiovascular Genetics and
INTRODUCTION Sino-German Laboratory for Molecular Medicine (X-XZ, S-HL, X-XL, and
RH) and the Department of Cardiology (X-XZ, Y-LX, S-HL, RH, and
Cardiovascular disease (CVD) is a leading cause of morbidity,
X-HH), Cardiovascular Institute and FuWai Hospital, Chinese Academy of
mortality, and disability worldwide (1). Hyperlipidemia, which Medical Sciences and Peking Union Medical College, Beijing, China.
results from abnormalities in lipid metabolism, leads to the 2
X-XZ and Y-LX contributed equally to this article.
development of atherosclerotic plaques and is one of the key risk 3
Supported by the Ministry of Science and Technology of China with
factors of CVD (2). Risk of heart attack is 3-fold higher in a grant of the National High-Tech Research and Development Program of
subjects with hyperlipidemia than in subjects with normal lipid China (to X-HH).
4
status (3), whereas a 1% decrease in serum cholesterol has been Address correspondence to X-Ho Huang, Cardiovascular Institute and Fu-
shown to reduce risk of CVD by 3% (1). With the increasing Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Med-
ical College, 167 Beilishilu, Beijing 100037, China. E-mail: huangxhong12@
incidence of hyperlipidemia, more and more consumers are
gmail.com; or R Hui, Cardiovascular Institute and FuWai Hospital, Chinese
aware of the effects of what they eat and drink on their blood lipid Academy of Medical Sciences and Peking Union Medical College, 167
profiles. Beilishilu, Beijing 100037, China. E-mail: huirutai@gmail.com.
Green tea is a widely consumed beverage worldwide and is Received December 21, 2010. Accepted for publication May 16, 2011.
traditionally used in Asian countries as a medication. Green tea is First published online June 29, 2011; doi: 10.3945/ajcn.110.010926.

Am J Clin Nutr 2011;94:601–10. Printed in USA. Ó 2011 American Society for Nutrition 601
602 ZHENG ET AL

METHODS trations were reported several times in different stages of the


trials, only final records of lipid concentrations at the end of the
Search strategy trials were extracted for the meta-analysis.
According to the Quality of Reporting of Meta-analyses, we
systematically searched PubMed (http://www.ncbi.nlm.nih.gov/
pubmed; from 1967 to August 2010), Embase (http://www.embase. Data synthesis and analysis
com; from December 1977 to 2010), the Cochrane Library database Net changes in each of the study variables, which were cal-
(http://www.cochrane.org), and reviews and reference lists of rel- culated from baseline and follow-up means and SDs (follow-up
evant articles by using the text key words tea, green tea, green tea minus baseline) were used to estimate the principle effect. When

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


extract, tea polyphenols, catechin, EGCG, and camelia sinensis, SDs were not directly available, they were calculated from SEs or
which were paired with the following words: blood lipid, blood CIs. In instances in which variances for net changes were not
cholesterol, low-density lipoprotein cholesterol, or high-density directly reported, they were calculated from CIs, P values, or
lipoprotein cholesterol. The search was restricted to English-lan- individual variances from the green tea group and control group.
guage reports of clinical trials in adult humans. In addition, For trials in which variances for paired differences were sepa-
a manual search of references from reports of clinical trials or rately reported for each group, a pooled variance for the net
review articles was performed to identify relevant trials. Attempts change was calculated by using standard methods. In addition, the
were also made to contact investigators for unpublished data. change-from-baseline SDs were also imputed by using correlation
coefficient methods referenced in the Cochrane Handbook for
Study selection Systematic Reviews of Interventions (26). We assumed a correla-
tion coefficient of 0.68 (26). For one study (12) in which medians
Studies were selected for this analysis if they met the following and interquartile ranges were reported, the width of the inter-
criteria: 1) subjects consumed a green tea beverage or extract for quartile range was ’1.35 SD, and the median was approximately
.2 wk, 2) the study was an RCT in human adults with either the mean (26).
a parallel or crossover design, 3) the starting and endpoint lipid Our meta-analysis and statistical analyses were performed with
concentrations (TC, LDL cholesterol, and HDL cholesterol) STATA (version 10; StataCorp, College Station, TX). Weighted
were available, 4) food-intake control regimens of experimental mean differences and 95% CIs were calculated for net changes in
groups were consistent with those of control groups, 5) green tea lipid values. The statistic heterogeneity of treatment effects be-
extract was not given as part of a multicomponent supplement in tween studies was formally tested with Cochran’s test (P , 0.1).
either experimental or control groups, and 6) blood samples The I2 statistic was also examined, and we considered I2 . 50%
were obtained from fasting subjects. to indicate significant heterogeneity between trials (27). Results
were obtained from a fixed-effects model if no significant het-
Quality assessment erogeneity was shown, and a random-effects model was selected
for the analysis if significant heterogeneity was shown (28).
The assessment of quality characteristics used the following Publication bias was assessed with funnel plots and the Egger’s
criteria 1) randomization, 2) concealment of treatment alloca- regression test. To examine the effects of factors on the primary
tion, 3) participant masking, 4) researcher masking, 5) reporting outcomes and identify the possible source of heterogeneity within
of withdrawals, 6) generation of random numbers, 7) and re- these studies, previously defined subgroup analyses were per-
porting of industry funding. The Jadad score was also introduced formed (type of intervention, catechins dose, health status, study
to evaluate the quality of the studies. Trials scored one point for duration, and Jadad score). Additional sensitivity analyses were
each area addressed in the study design (randomization, blind- also performed according to the Cochrane Handbook for Sys-
ing, concealment of allocation, reporting of withdrawals, and tematic Reviews of Interventions (26).
generation of random numbers) with a possible score of between
0 and 5 (highest level of quality) (25). Higher numbers repre-
sented a better quality (Jadad score 4).
RESULTS

Data extraction Results of literature search


The search, data extraction, and quality assessment were The method used to select studies is shown in Figure 1. A total
completed independently by 2 reviewers (X-XZ and Y-LX) of 805 potentially eligible articles were initially identified, and
according to inclusion criteria. Any discrepancies between the 2 778 articles were excluded because they were not clinical trials
reviewers were resolved through a discussion until a consensus or the interventions were not relevant to the purpose of the
was reached. Study characteristics (including authors, publica- current meta-analysis. Therefore, 27 potentially relevant articles
tion year, sample size, study design, study duration, dose, and were selected for detailed evaluation (11–24, 29–41). From the
type of intervention), population information (sex and initial overall pool of full-text articles, 13 articles were excluded from
healthy status), and baseline and final concentrations or net the analysis. The duration of the experiment was ,2 wk for 5 of
changes of TC, LDL cholesterol, and HDL cholesterol were the trials (31, 32, 36, 39, 40), whereas 3 of the trials did not
extracted. Extracted data were converted to conventional units report relevant outcomes (29, 37, 38). Three articles lacked
(eg, for TC concentrations, 1 mmol/L converted to 38.6 mg/dL). sufficient details for inclusion in meta-analysis (34, 35, 41). In
For multiarm studies, only intervention groups that met inclusion one study, blood samples were collected from subjects who were
criteria were used in this analysis (26). If blood lipid concen- not fasting (30). Another article was excluded because a low-fat
GREEN TEA LOWERS CHOLESTEROL 603
usual lifestyles of participants. In 3 trials (17, 18, 23) of the in-
cluded 14 trials, mild side effects were reported such as mild skin
rashes, gastric upset, abdominal bloating. No side effects were
reported in 7 trials (12, 14, 15, 19, 20, 22, 24). In the remaining 4
trials (11, 13, 16, 21), reports of side effects were unclear.

Data quality
Results of the validity of included trials are presented in Table

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


2. The study qualities of selected trials were diverse; 3 trials (12,
17, 20) were classified as high quality (Jadad score 4) and 11
trials (11, 13–16, 18–22, 24) were low quality (Jadad score of 2
or 3). Allocation concealment was clearly adequate in only one
study (17). Two trials (12, 17) reported the generation of random
numbers. Details of dropouts were reported in 12 trials (12, 14–
24). Two studies (19, 20) received industry funding.

Effect of green tea on lipid concentrations


Primary outcome measures were changes in TC, LDL cho-
lesterol, HDL cholesterol between baseline and final concen-
trations because of green tea beverage and green tea extract
supplementation. The results for TC were reported in 14 com-
parisons from 13 studies that represented 949 participants, and the
mean change in TC concentrations was significantly reduced in
subjects supplemented with green tea (27.20 mg/dL; 95% CI:
28.19, 26.21 mg/dL; P , 0.001) than in controls. Heterogeneity
was not shown for this outcome (heterogeneity chi-square 14.30,
I2 = 9.1%, P = 0.353; Figure 2). The mean change in LDL-
cholesterol concentrations was reported in 11 comparisons from
FIGURE 1. Flowchart showing the number of citations retrieved by 10 studies that represented 853 participants and was significantly
individual searches of trials included in the review.
decreased by 2.19 mg/dL (95% CI: 23.16, 21.21 mg/dL; P ,
0.001) in intervention groups than in control arms. No heteroge-
diet was only used in the control group, and the results may have neity was observed for this outcome (heterogeneity chi-square =
been confounded by the inappropriate study design (33). 13.41, I2 = 25.4%, P = 0.201; Figure 3). The results of blood
HDL cholesterol were calculated in 12 comparisons from 11
studies that included 998 subjects. For intervention groups, the
Study characteristics mean change in blood HDL-cholesterol concentrations showed
Fourteen eligible RCTs with 1136 subjects were enrolled in the a favorable trend, but it was not significant (+0.25 mg/dL; 95%
meta-analysis (11–24). Characteristics of the trials are shown in CI: 20.73, 1.23 mg/dL; P = 0.62). No heterogeneity was detected
Table 1. The work of Princern et al (24) was separated into 2 for this outcome (heterogeneity chi-square = 13.36, I2 = 17.7%,
trials (effects of green tea beverage and green tea extract on P = 0.270; Figure 4).
plasma lipid profiles). The trials varied in size from 20 to 240 Subgroup analyses were conducted to explore the dose-effect
subjects. The study duration varied from 3 wk to 3 mo (median: relation, study-duration effects, health-status effects, as well as
12 wk). Doses of green tea catechins in the treatment group differences between drinking green tea and taking green tea
ranged from 150 to 2500 mg/d (median: 625 mg/d). Of the 14 extracts. The consumption of catechins was divided into low dose
trials used in the meta-analysis, 5 trials were conducted in healthy (,625 mg/d) and high dose (625 mg/d). The time to follow-up
adults (14, 15, 22–24), and 5 trials were conducted in overweight for the assessment of lipid-lowering therapy varied from 3 wk to
to obese adults (12, 13, 17, 18, 21). The other studies investigated 3 mo, and thus, a subgroup analysis was performed by dividing
the effects of green tea consumption in patients with cardiovas- the follow-up duration into a shorter-term subgroup (,12 wk)
cular risks such as hypercholesterolemia (11, 19) or diabetes (16, and a longer-term subgroup (12 wk).
20). A green tea beverage was tested in one-half of trials (7 of 14 Subgroup analyses showed that significant reductions of TC and
trials; 11, 16, 17, 19–21, 23), and a green tea extract capsule was LDL cholesterol were not influenced by the type of intervention
used in the remaining 7 trials (12–15, 18, 22, 24). Most of the (drinking green tea or taking green tea supplement). Analyses also
trials (12 trials) adopted parallel study designs (12–15, 17–24), showed that TC and LDL cholesterol were significantly decreased
whereas 2 trials used crossover designs (11, 16). Twelve trials in the lower– and higher–catechin consumption groups. Green tea
were double-blinded trials (11–15, 17–23), and 10 trials were significantly reduced TC and LDL cholesterol in healthy subjects
placebo-controlled trials (11–15, 17–19, 23, 24). A low-fat diet and in participants with cardiovascular risks. In the shorter- and
was fed in 2 trials (11, 19), and one trial used a low-energy diet longer-term subgroups, significant reductions in TC and LDL
(13). In the other trials, investigators attempted to maintain the cholesterol were shown. We also stratified studies according to the
TABLE 1 604
Characteristics of 14 included randomized controlled trials1
Author, publication year Study No. of Side
(reference no.) design subjects (M/F) Population Duration Tea group Control group effect Concurrent lifestyle modification

Batista et al, 2009 (11) Double-blinded 33 (5/28) Hypercholesterolemic 8 wk 250 mg GTE capsules Placebo capsules NR Maintain low-fat diet; no vitamin
crossover patients, 21–71 y (catechins NR) supplement
of age
Chan et al, 2006 (12) Double-blinded 34 (0/34) Obese women with 3 mo Green tea capsules Placebo capsules No Limit caffeine; nutritional consults
parallel PCOS, 25–40 y (661 mg catechins)
of age
Diepvens et al, 2006 Double-blinded 46 (0/46) Overweight women, 12 wk GTE capsules (1207 Placebo (maltodextrin) NR Maintain low-energy diet; limit 3
(13) parallel 19–57 y of age mg catechins) capsules cups of coffee/d
Frank et al, 2009 (14) Double-blinded 33 (33/0) Healthy men, 18–55 y 3 wk Aqueous GTE capsule Placebo (maltodextrin) No Maintain usual diet and exercise,
parallel of age (714 mg catechins) capsules limit tea and coffee 3 cups/d
Freese et al, 1999 (15) Double-blinded 20 (0/20) Healthy nonsmoking 4 wk 3 g GTE capsules Placebo (saccharose, No Rich in linoleic acid diet
parallel women, 23–50 y (810 mg catechins) microcrystalline,
of age cocoa) capsules
Fukino et al, 2008 (16) Open-label 60 (51/9) Patients with diabetes 2 mo GTE powder packets No intervention NR Maintain usual diet
crossover or prediabetes, 32–73 y (456 mg catechins)
of age
Hsu et al, 2008 (17) Double-blinded 78 (0/78) Obese women, 16–60 y 12 wk 1200 mg GTE capsules Placebo (cellulose) Yes Maintain normal diet
parallel of age (491 mg catechins) capsules
Maki et al, 2009 (18) Double-blinded 128 (67/61) Overweight or obese 12 wk 500 mL green tea Placebo beverage Yes Maintain normal diet, limit 2
parallel adults, total cholesterol beverage (625 mg caffeinated beverages/d
200 mg/dL, 21–65 y catechins)
of age
Maron et al, 2003 (19) Double-blinded 220 Patients with mild- 12 wk 375 mg GTE capsule Placebo (inert No Maintain low–saturated fat diet
ZHENG ET AL

parallel to-moderate (150 mg catechins) ingredients) capsules


hypercholesterolemia
Nagao et al, 2009 (20) Double-blinded 43 (18/25) Patients with diabetes 12 wk 340 mL green tea 340 mL green tea No Maintain usual diet and exercise
parallel (583 mg catechins) (96 mg catechins)
Nagao et al, 2007 (21) Double-blinded 240 (140/100) Adults with visceral 12 wk 340 mL green tea 340 mL green tea NR Maintain usual diet and exercise;
parallel fat-type obesity, 25–55 y beverage (583 mg beverage (96 mg limit medications or supplements
of age catechins) catechins) that influence lipid or carbohydrate
metabolism
Nagao et al, 2005 (22) Double-blinded 35 (35/0) Healthy men, 24–46 y 12 wk 340 mL GTE/oolong tea 340 mL oolong tea No 2 planned meals/d; no tea or food
parallel of age beverage (690 mg beverage (22 mg high in catechins
catechins) catechins)
Nantz et al, 2009 (23) Double-blinded 108 (44/64) Healthy, 21–50 y of age 3 wk 400 mg GTE capsules Placebo (maltodextrin) Yes Maintain normal diet and exercise;
parallel (320 mg catechins) capsules limit tea 1 cup/d
Princen et al, 1998 (24) Single-blinded 30 (15/15) Healthy, 34 6 12 y 4 wk 900 mL green tea Placebo (mineral water) No Limit milk in tea, 2 cups of fruit
parallel of age (852 mg catechins) juice or tea, 2 oranges daily
Princen et al, 1998 (24) Single-blinded 28 (13/15) Healthy, 34 6 12 y 4 wk 9 g GTE capsules Placebo (mineral water) No Limit milk in tea, 2 cups of fruit
parallel of age (2500 mg catechins) juice or tea, 2 oranges daily
1
GTE, green tea extract; NR, not reported; PCOS, polycystic ovarian syndrome.

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


GREEN TEA LOWERS CHOLESTEROL 605
TABLE 2
Validity of included studies
Allocation Masking of Masking of Generation of random Reporting of Industry Jadad
Reference concealment participants researchers number reported withdrawals funding score

Batista et al (11) Unclear Yes Yes No No No 2


Chan et al (12) Inadequate Yes Yes Yes Yes No 4
Diepvens et al (13) Unclear Yes Yes No No No 2
Frank et al (14) Unclear Yes Yes No Yes No 3
Freese et al (15) Unclear Yes Yes No Yes No 3

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


Fukino et al (16) Unclear No No No Yes No 2
Hsu et al (17) Adequate Yes Yes Yes Yes No 5
Maki et al (18) Unclear Yes Yes No Yes No 3
Maron et al (19) Inadequate Yes Yes No Yes Yes 3
Nagao et al (20) Unclear Yes Yes No Yes Yes 3
Nagao et al (21) Inadequate Yes Yes No Yes No 3
Nagao et al (22) Unclear Yes Yes No Yes No 3
Nantz et al (23) Unclear Yes Yes Yes Yes No 4
Princen et al (24) Unclear Yes No No Yes No 2

Jadad score (,4 or 4). Significant reductions in TC and LDL Sensitivity analysis showed that the significance in the pooled
cholesterol were shown in the low- and high-score subgroups. No changes in TC, LDL cholesterol, and HDL cholesterol were not
significant changes in HDL cholesterol were observed in any altered after the imputation correlation coefficient of 0.5. Sensitivity
subgroup. Results are summarized in Table 3. analysis that excluded low-quality studies (11, 13–16, 18–22, 24)

FIGURE 2. Meta-analysis of effects of green tea consumption on total cholesterol (TC) compared with control arms. Sizes of data markers indicate the
weight of each study in the analysis. WMD, weighted mean difference (the result was obtained from a fixed-effects model).
606 ZHENG ET AL

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


FIGURE 3. Meta-analysis of effects of green tea consumption on LDL cholesterol compared with control arms. Sizes of data markers indicate the weight of
each study in the analysis. WMD, weighted mean difference (the result was obtained from a fixed-effects model).

showed that significant results were not influenced concerning TC, showed that these changes were not influenced by the type of
LDL cholesterol, and HDL cholesterol [TC concentration: 23.05 intervention, treatment doses of green tea catechins, study du-
mg/dL (95% CI: 26.62, 0.53 mg/dL), P 0.758; LDL-cholesterol ration, individual health status, or quality of the study.
concentration: 25.25 mg/dL (95% CI: 28.54, 21.95 mg/dL), A large population-based study that involved .40,000 middle-
P = 0.053; HDL-cholesterol concentration: 2.36 mg/dL (95% aged Japanese revealed that, compared with no tea drinking,
CI: 20.36, 5.08 mg/dL); P = 0.833]. The removal of 2 trials (19, habitual green tea consumption [an average of .2 cups (’17
20) with industry funding did not change the final results [TC oz)/d for 10 y] was associated with a lower risk of death from
concentration: 27.16 mg/dL (95% CI: 28.16, 26.17 mg/dL); CVD (5). The beneficial effects of green tea on cardiovascular
P = 0.359; LDL-cholesterol concentration: 22.19 mg/dL (95% health may be due to the high concentration of green tea cat-
CI: 23.16, 21.21 mg/dL); P = 0.201; HDL-cholesterol con- echins, which have been proven to favorably modulate the
centration: 0.06 mg/dL (95% CI: 20.98, 1.11 mg/dL); P = plasma lipid profile. These small molecules exert a variety of
0.263]. The results are also shown in Table 3. Overall, no sig- physiologic actions and, thus, affect lipid metabolism.
nificant heterogeneity was shown for TC, LDL cholesterol, and Animal experiments indicated that the inhibition of cholesterol
HDL cholesterol, and the results were reported on the basis of absorption may be the mechanism to explain the cholesterol-
fixed-effects models. lowering effects of green tea. Catechins with gallate esters were
shown to interfere with the biliary micelle system in the lumen of
the intestine by forming insoluble co-precipitates of cholesterol
Publication bias and increasing the fecal excretion of cholesterol (42). This ap-
Funnel plots and Egger’s tests indicated no significant publi- parent decrease in cholesterol absorption and reduction in liver
cation bias in the meta-analyses of TC, LDL cholesterol, and HDL cholesterol concentrations lead to an increase of LDL-receptor
cholesterol (TC Egger’s test: P = 0.148; LDL cholesterol Egger’s expression and activity (9). This cell-surface protein is present on
test: P = 0.385; HDL cholesterol Egger’s test: P = 0.679). the outer surface of most cells, but in particular liver cells, it can
remove cholesterol-carrying LDL from the circulation. Studies in
animals have provided evidence that green tea extracts and their
DISCUSSION catechin constituents can reduce plasma, liver, and thoracic aorta
Our meta-analysis showed that both green tea beverages and cholesterol and up-regulate hepatic LDL receptors (9, 10). Bursill
green tea extract supplementation significantly reduce blood TC and Roach (9) and Bursill et al (10) have concluded that the
and LDL-cholesterol concentrations but did not affect HDL administration of green tea extract was able to significantly in-
cholesterol concentrations. Subgroup and sensitivity analyses crease both the LDL-receptor binding activity and relative
GREEN TEA LOWERS CHOLESTEROL 607

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


FIGURE 4. Meta-analysis of the effects of green tea consumption on HDL cholesterol as compared with the control arms. Sizes of the data markers
indicate the weight of each study in the analysis. WMD, weighted mean difference (the result was obtained from a fixed-effects model).

amounts of LDL-receptor protein. In addition, there is another trations (12, 13, 16, 24). To clarify the precise effect of green tea on
possible major mechanism by which green tea lowers cholesterol: serum cholesterol, we conducted the current meta-analysis of
catechins have direct inhibitory effects on cholesterol synthesis. published RCTs. The results indicated that green tea beverages and
A recent in vitro study has revealed that green tea catechins were green tea extract supplementation significantly reduced TC and
potent and selective inhibitors of squalene epoxidase, which is LDL-cholesterol concentrations. The results of this study were
likely a rate-limiting enzyme of cholesterol biosynthesis (43). consistent with a recently published meta-analysis that showed that
These effects of green tea are similar to hypocholesterolemic green tea significantly reduced LDL-cholesterol concentrations
drugs such as statins, which reduce cholesterol synthesis and (45). Furthermore, a recent study conducted in Japanese children
increase the LDL receptor (44). showed that the consumption of a catechin-rich beverage for 24 wk
The effect of green tea beverages and green tea extract on blood significantly decreased LDL cholesterol after a 12-wk follow-up
lipid profiles has been investigated in vitro and in vivo, including in (46). To our knowledge, this study provided new evidence, which
studies in both animals and humans, by many researchers. Hsu et al supported the conclusion of our meta-analysis, that green tea has
(17) have revealed that green tea intakes significantly decreased hypocholesterolemic properties.
LDL-cholesterol concentrations and markedly increased concen- These results suggested that green tea may be incorporated into
trations of HDL cholesterol. Consistent with this study, other a targeted dietary program as part of public health policy to im-
studies showed that green tea consumption was able to reduce prove cardiovascular health. Because most Americans drink high-
serum cholesterol concentrations (11, 14, 19, 21, 23). In contrast, calorie beverages or alcohol on a daily basis, and only 20% of
several studies reported that there were no positive correlations Americans consume low-calorie green tea (47), the potential for
between green tea intake and reduced blood cholesterol concen- meaningful intervention is real.
608

TABLE 3
Subgroup analyses of total, LDL, and HDL cholesterol stratified by previously defined study characteristics
Total cholesterol LDL cholesterol HDL cholesterol

No. of Mean difference P for No. of Mean difference P for No. of Mean difference P for
Variables trials (95% CI) heterogeneity trials (95% CI) heterogeneity trials (95% CI) heterogeneity

mg/dL mg/dL mg/dL


Subgroup analysis
Type of intervention
Green tea beverage 6 27.56 (28.61, 26.52) 0.288 5 21.82 (22.86, 20.78) 0.549 5 20.57 (21.93, 0.78) 0.229
Green tea capsule 8 23.89 (27.05, 20.72) 0.843 6 25.19 (28.15, 22.23) 0.313 7 1.16 (20.27, 2.58) 0.576
Catechins dose
,625 mg/d (low median) 6 23.51 (26.41, 20.61) 0.726 5 25.36 (27.99, 22.73) 0.796 5 0.07 (21.14, 1.29) 0.236
625 mg/d (high median) 8 27.69 (28.75, 26.64) 0.731 6 21.68 (22.73, 20.62) 0.388 7 0.57 (21.09, 2.23) 0.270
Healthy status
Healthy 6 23.26 (26.61, 0.08) 0.809 4 25.28 (28.14, 22.14) 0.710 4 20.49 (22.84, 1.87) 0.784
ZHENG ET AL

With cardiovascular risks 8 27.58 (28.62, 26.54) 0.519 7 21.85 (22.88, 20.83) 0.246 8 0.40 (20.68, 1.48) 0.106
Duration
,12 wk (low median) 7 23.19 (26.40, 0.02) 0.899 5 24.77 (27.77, 21.77) 0.742 5 0.05 (21.80, 1.90) 0.650
12 wk (high median) 7 27.63 (28.67, 26.58) 0.489 6 21.88 (22.91, 20.85) 0.142 7 0.32 (20.83, 1.48) 0.094
Jadad score
Low (2 or 3) 11 27.55 (28.58, 26.52) 0.617 8 21.89 (22.92, 20.87) 0.789 10 20.07 (21.12, 0.98) 0.300
High (4 or 5) 3 23.05 (26.62, 0.53) 0.758 3 25.25 (28.54, 21.95) 0.053 3 2.36 (20.36, 5.08) 0.833
Sensitivity analysis
High-quality studies 3 23.05 (26.62, 0.53) 0.758 3 25.25 (28.54, 21.95) 0.053 3 2.36 (20.36, 5.08) 0.833
Studies did not receive industry funding 13 27.16 (28.16, 26.17) 0.359 11 22.19 (23.16, 21.21) 0.201 11 0.06 (20.98, 1.11) 0.263

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


GREEN TEA LOWERS CHOLESTEROL 609
Although we believe that the current meta-analysis provided 3. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable
useful information, some potential limitations should be addressed. risk factors associated with myocardial infarction in 52 countries (the
INTERHEART study): case-control study. Lancet 2004;364:937–52.
First, an obvious source of conflict was that there is no general 4. Balentine DA, Wiseman SA, Bouwens LC. The chemistry of tea fla-
agreement on what quantity constitutes a cup of green tea. Doses of vonoids. Crit Rev Food Sci Nutr 1997;37:693–704.
green tea catechins in the 14 trials involved in our meta-analysis 5. Kuriyama S, Shimazu T, Ohmori K, et al. Green tea consumption and
ranged from 150 to 2500 mg/d (median: 625 mg/d). The wide mortality due to cardiovascular disease, cancer, and all causes in Japan:
the Ohsaki study. JAMA 2006;296:1255–65.
range of green tea catechin doses made it difficult to determine the 6. Imai K, Nakachi K. Cross sectional study of effects of drinking green
optimal dose that would most improve the blood lipid profile. tea on cardiovascular and liver diseases. BMJ 1995;310:693–6.
Second, caffeine is naturally contained in green tea. A newly 7. Stangl V, Dreger H, Stangl K, Lorenz M. Molecular targets of tea

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


released study showed that coffee consumption led to an increase polyphenols in the cardiovascular system. Cardiovasc Res 2007;73:
348–58.
in serum concentrations of TC and HDL cholesterol, mainly 8. Koo SI, Noh SK. Green tea as inhibitor of the intestinal absorption of
because of caffeine (48). In our meta-analysis, 11 trials stated that lipids: potential mechanism for its lipid-lowering effect. J Nutr Bio-
green tea beverages or extracts contained caffeine in the in- chem 2007;18:179–83.
tervention groups. The independent effect of caffeine might have 9. Bursill CA, Roach PD. A green tea catechin extract upregulates the
been a confounding factor that influenced the results of this meta- hepatic low-density lipoprotein receptor in rats. Lipids 2007;42:621–7.
10. Bursill CA, Abbey M, Roach PD. A green tea extract lowers plasma
analysis. cholesterol by inhibiting cholesterol synthesis and upregulating the
Third, the quality of the trials included in our meta-analysis LDL receptor in the cholesterol-fed rabbit. Atherosclerosis 2007;193:
varied from low to high. Of the 14 trials, only 3 trials (12, 17, 23) 86–93.
were high-quality studies (Jadad score 4), whereas the other 11. Batista Gde A, Cunha CL, Scartezini M, von der Heyde R, Bitencourt
MG, Melo SF. Prospective double-blind crossover study of Camellia
studies were low quality. Meanwhile, the study durations were sinensis (green tea) in dyslipidemias. Arq Bras Cardiol 2009;93:
short (from 3 wk to 3 mo). Therefore, more high-quality and long- 128–34.
term (over years) randomized studies are needed in the future. 12. Chan CC, Koo MW, Ng EH, Tang OS, Yeung WS, Ho PC. Effects of
Fourth, our meta-analysis did not pool safety data because no Chinese green tea on weight, and hormonal and biochemical profiles in
obese patients with polycystic ovary syndrome–a randomized place-
serious side effects were reported in these involved trials. However, bo-controlled trial. J Soc Gynecol Investig 2006;13:63–8.
concern has been raised as to the safety of supplementation with 13. Diepvens K, Kovacs EM, Vogels N, Westerterp-Plantenga MS. Meta-
high doses of green tea polyphenols. In mice, the intraperitoneal bolic effects of green tea and of phases of weight loss. Physiol Behav
injection of green tea catechins increased plasma concentrations of 2006;87:185–91.
14. Frank J, George TW, Lodge JK, et al. Daily consumption of an aqueous
alanine transaminase (49). In addition, clinical reports have shown
green tea extract supplement does not impair liver function or alter
that green tea was the major dietary source of oxalate in some cardiovascular disease risk biomarkers in healthy men. J Nutr 2009;
patients who presented with kidney oxalate stones (50). Daily 139:58–62.
green tea consumption in the current meta-analysis was equivalent 15. Freese R, Basu S, Hietanen E, et al. Green tea extract decreases plasma
to 18 cups, and the trials varied in length from 3 wk to 3 mo, malondialdehyde concentration but does not affect other indicators of
oxidative stress, nitric oxide production, or hemostatic factors during
and no subjects experienced major adverse events. This phe- a high-linoleic acid diet in healthy females. Eur J Nutr 1999;38:
nomenon may be attributed to the following 2 factors: 1) the 149–57.
durations of studies involved in our meta-analysis were not long 16. Fukino Y, Ikeda A, Maruyama K, Aoki N, Okubo T, Iso H. Random-
enough to observe serious side effects, and 2) consumption of ized controlled trial for an effect of green tea-extract powder supple-
mentation on glucose abnormalities. Eur J Clin Nutr 2008;62:953–60.
,18 cups of green tea/d may be not enough to cause adverse 17. Hsu CH, Tsai TH, Kao YH, Hwang KC, Tseng TY, Chou P. Effect of
effects. Therefore, safety issues need to be evaluated in the future green tea extract on obese women: a randomized, double-blind, pla-
under conditions of long-term and high-dose exposure. cebo-controlled clinical trial. Clin Nutr 2008;27:363–70.
In conclusion, green tea significantly reduced serum total and 18. Maki KC, Reeves MS, Farmer M, et al. Green tea catechin con-
sumption enhances exercise-induced abdominal fat loss in overweight
LDL-cholesterol concentrations, and the changes were not influenced and obese adults. J Nutr 2009;139:264–70.
by the type of intervention, treatment doses of green tea catechins, 19. Maron DJ, Lu GP, Cai NS, et al. Cholesterol-lowering effect of a
study duration, individual health status, or quality of the study. For theaflavin-enriched green tea extract: a randomized controlled trial.
intervention groups, the mean change in blood HDL-cholesterol Arch Intern Med 2003;163:1448–53.
20. Nagao T, Meguro S, Hase T, et al. A catechin-rich beverage improves
concentrations showed a favorable trend, but it was not significant.
obesity and blood glucose control in patients with type 2 diabetes.
We thank Lei Jia for her assistance and BioMed Proofreading for their text Obesity (Silver Spring) 2009;17:310–7.
21. Nagao T, Hase T, Tokimitsu I. A green tea extract high in catechins
editing.
reduces body fat and cardiovascular risks in humans. Obesity (Silver
The authors’ responsibilities were as follows—X-XZ, Y-LX, RH, and
Spring) 2007;15:1473–83.
X-HH: conceived the idea of the study and designed the study strategy; 22. Nagao T, Komine Y, Soga S, et al. Ingestion of a tea rich in catechins
X-XZ and Y-LX: summarized data and conducted data analyses; and all leads to a reduction in body fat and malondialdehyde-modified LDL in
authors: contributed to data analyses and the writing and revision of the man- men. Am J Clin Nutr 2005;81:122–9.
uscript. None of the authors declared a conflict of interest. 23. Nantz MP, Rowe CA, Bukowski JF, Percival SS. Standardized cap-
sule of Camellia sinensis lowers cardiovascular risk factors in a ran-
domized, double-blind, placebo-controlled study. Nutrition 2009;25:
147–54.
REFERENCES 24. Princen HM, van Duyvenvoorde W, Buytenhek R, et al. No effect of
1. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke consumption of green and black tea on plasma lipid and antioxidant
statistics–2010 update: a report from the American Heart Association. levels and on LDL oxidation in smokers. Arterioscler Thromb Vasc
Circulation 2010;121:e46–e215. Biol 1998;18:833–41.
2. Jain KS, Kathiravan MK, Somani RS, Shishoo CJ. The biology 25. Moher D, Pham B, Jones A, et al. Does quality of reports of rando-
and chemistry of hyperlipidemia. Bioorg Med Chem 2007;15: mised trials affect estimates of intervention efficacy reported in meta-
4674–99. analyses? Lancet 1998;352:609–13.
610 ZHENG ET AL
26. Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews 39. van het Hof KH, Wiseman SA, Yang CS, Tijburg LB. Plasma and li-
of interventions. Version 5.0.2. New York, NY: Wiley, 2009. poprotein levels of tea catechins following repeated tea consumption.
27. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring in- Proc Soc Exp Biol Med 1999;220:203–9.
consistency in meta-analyses. BMJ 2003;327:557–60. 40. Dulloo AG, Duret C, Rohrer D, et al. Efficacy of a green tea extract
28. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin rich in catechin polyphenols and caffeine in increasing 24-h energy
Trials 1986;7:177–88. expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70:
29. Hursel R, Westerterp-Plantenga MS. Green tea catechin plus caffeine 1040–5.
supplementation to a high-protein diet has no additional effect on body 41. Basu A, Sanchez K, Leyva MJ, et al. Green tea supplementation affects
weight maintenance after weight loss. Am J Clin Nutr 2009;89:822–30. body weight, lipids, and lipid peroxidation in obese subjects with
30. Eichenberger P, Colombani PC, Mettler S. Effects of 3-week consumption metabolic syndrome. J Am Coll Nutr 2010;29:31–40.
of green tea extracts on whole-body metabolism during cycling exercise in 42. Chan PT, Fong WP, Cheung YL, Huang Y, Ho WK, Chen ZY. Jasmine

Downloaded from https://academic.oup.com/ajcn/article-abstract/94/2/601/4597944 by KERIS National Access user on 21 January 2020


endurance-trained men. Int J Vitam Nutr Res 2009;79:24–33. green tea epicatechins are hypolipidemic in hamsters (Mesocricetus
31. Dean S, Braakhuis A, Paton C. The effects of EGCG on fat oxidation auratus) fed a high fat diet. J Nutr 1999;129:1094–101.
and endurance performance in male cyclists. Int J Sport Nutr Exerc 43. Abe I, Seki T, Umehara K, et al. Green tea polyphenols: novel and
Metab 2009;19:624–44. potent inhibitors of squalene epoxidase. Biochem Biophys Res Com-
32. Panza VS, Wazlawik E, Ricardo Schutz G, Comin L, Hecht KC, da mun 2000;268:767–71.
Silva EL. Consumption of green tea favorably affects oxidative stress 44. Endo A. The discovery and development of HMG-CoA reductase in-
markers in weight-trained men. Nutrition 2008;24:433–42. hibitors. J Lipid Res 1992;33:1569–82.
33. Bertipaglia de Santana M, Mandarino MG, Cardoso JR, et al. Asso- 45. Hooper L, Kroon PA, Rimm EB, et al. Flavonoids, flavonoid-rich
ciation between soy and green tea (Camellia sinensis) diminishes hy- foods, and cardiovascular risk: a meta-analysis of randomized con-
percholesterolemia and increases total plasma antioxidant potential in trolled trials. Am J Clin Nutr 2008;88:38–50.
dyslipidemic subjects. Nutrition 2008;24:562–8. 46. Matsuyama T, Tanaka Y, Kamimaki I, Nagao T, Tokimitsu I. Catechin
34. Inami S, Takano M, Yamamoto M, et al. Tea catechin consumption reduces safely improved higher levels of fatness, blood pressure, and choles-
circulating oxidized low-density lipoprotein. Int Heart J 2007;48:725–32. terol in children. Obesity (Silver Spring) 2008;16:1338–48.
35. Erba D, Riso P, Bordoni A, Foti P, Biagi PL, Testolin G. Effectiveness 47. Vogelzang JL. New dietary guidelines to help Americans make better
of moderate green tea consumption on antioxidative status and plasma food choices and live healthier lives. Home Healthc Nurse 2005;23:
lipid profile in humans. J Nutr Biochem 2005;16:144–9. 399–401.
36. Berube-Parent S, Pelletier C, Dore J, Tremblay A. Effects of encap- 48. Kempf K, Herder C, Erlund I, et al. Effects of coffee consumption on
sulated green tea and Guarana extracts containing a mixture of epi- subclinical inflammation and other risk factors for type 2 diabetes:
gallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat a clinical trial. Am J Clin Nutr 2010;91:950–7.
oxidation in men. Br J Nutr 2005;94:432–6. 49. Galati G, Lin A, Sultan AM, O’Brien PJ. Cellular and in vivo hepa-
37. Hodgson JM, Croft KD, Mori TA, Burke V, Beilin LJ, Puddey IB. totoxicity caused by green tea phenolic acids and catechins. Free Radic
Regular ingestion of tea does not inhibit in vivo lipid peroxidation in Biol Med 2006;40:570–80.
humans. J Nutr 2002;132:55–8. 50. Gasinska A, Gajewska D. Tea and coffee as the main sources of oxalate
38. Hodgson JM, Puddey IB, Croft KD, et al. Acute effects of ingestion of black in diets of patients with kidney oxalate stones. Rocz Panstw Zakl Hig
and green tea on lipoprotein oxidation. Am J Clin Nutr 2000;71:1103–7. 2007;58:61–7.

Vous aimerez peut-être aussi